title: Beta-asarone attenuates beta-amyloid-induced apoptosis through the inhibition of the activation of apoptosis signal-regulating kinase 1 in SH-SY5Y cells.
abstract: Beta-amyloid (Abeta) toxicity has been postulated to initiate synaptic loss and subsequent neuronal degeneration seen in Alzheimer's disease (AD). We previously demonstrated that beta-asarone improves cognitive function by suppressing neuronal apoptosis in vivo. In this study, we assessed the neuroprotective effects of beta-asarone against the toxicity of Abeta in relation to the mitochondria-mediated cell death process, and to elucidated the role of the ASK1/MKK7/JNK and mitochondrial pathways in beta-asarone-induced neuroprotection in SH-SY5Y cells. Our results show that beta-asarone afforded protection against Abeta-induced toxicity by inhibiting apoptosis in SH-SY5Y cells. This result was also confirmed by caspase-9 and caspase-3 activity assays. Expression of p-ASK1, p-MKK7, p-JNK, Bax, Bad, and cytochrome c release decreased after pretreatment with beta-asarone in SH-SY5Y cells exposed to A1-42. Interestingly, these effects of beta-asarone against Abeta1-42 insult were enhanced by ASK1 siRNA. These findings suggest that beta-asarone prevents Abeta1-42-induced neurotoxicity through attenuating neuronal apoptosis, and might be a potential preventive or therapeutic agent for AD.
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, Qiqihar, China.
authors.forename: De-Jia
authors.initials: DJ
authors.lastname: Zou
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Liu
authors.forename: Miao-Xian
authors.initials: MX
authors.lastname: Dong
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Li
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Ying-Cai
authors.initials: YC
authors.lastname: Niu
mesh_terms: D000081248:Allylbenzene Derivatives; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000840:Anisoles / Q000494:pharmacology*; D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents; D016759:Oncogene Protein p65(gag-jun) / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000081248:Allylbenzene Derivatives; D016229:Amyloid beta-Peptides; D000840:Anisoles; D017304:Annexin A5; D018696:Neuroprotective Agents; D016759:Oncogene Protein p65(gag-jun); D034741:RNA, Small Interfering; C012195:asarone; D012313:RNA; D048848:MAP Kinase Kinase Kinase 5; D016650:Fluorescein-5-isothiocyanate